Identification of genetic variants associated with lupus nephritis in a Taiwanese cohort through systematic genetic screening

通过系统性基因筛查,鉴定台湾人群中与狼疮性肾炎相关的遗传变异

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Abstract

Lupus nephritis (LN) is a common manifestation of systemic lupus erythematosus (SLE), affecting about half of the patients. This research uses genotype-phenotype associations to identify genetic markers, enhancing our understanding of LN pathogenesis. This study used genotype-phenotype association to explore genetic variants linked to LN in a Taiwanese cohort from the Taiwan Precision Medicine Initiative (TPMI). Genotyping was performed on 244 SLE and 63 LN patients using the TPM array. Genomic DNA underwent quality control via the Axiom Analysis Suite. Chi-squared tests identified significant variants, which were annotated and assessed for functional impacts using the 1000 Genomes Project, gnomAD, enabling comprehensive genetic analysis. This study on a Taiwanese cohort (LN, SLE, LN/SLE) identified four significant genetic variants (p-values < 10(-6)) associated with LN: rs1025129 in HGF, rs80282109 in BACH2, rs516119 in SOX1, and rs134545 in TTC28. These variants may affect LN pathogenesis through splicing junction changes and gene expression regulation, highlighting their potential as biomarkers. Our research identified four novel variants (rs134545, rs516119, rs1025129, rs80282109) in LN patients through a genotype-phenotype study on a Taiwanese population, suggesting their roles in LN pathogenesis and supporting their potential as new disease biomarkers.

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